To evaluate a potential role of an autocrine mechanism in gastric cancer, we carried out an immunohistochemical study of epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and epidermal growth factor receptor (EGFR) in 167 primary gastric cancer tissues. Slot blot hybridization was also performed to detect the amplification of EGFR gene. Immunohistochemically, 70 (42%), 87 (52%), 68 (41%) of 167 primary gastric cancers were stained positively for EGF, TGFalpha, and EGFR, respectively. Tumors with synchronous expression of EGFR and its ligands were most frequent in the following clinicopathological groups: tumors greater than 6 cm in size, those of the infiltrating type, and those of the poorly differentiated type. Among poorly differentiated carcinomas, the synchronous expression of EGFR and its ligands was more frequent in the infiltrating gross type than in the localized type. EGFR gene amplification was found in 5 (4.9%) of 103 primary tumors. EGFR gene amplification was also observed more frequently in infiltrating gross type of poorly,differentiated adenocarcinomas, as compared to localized gross type. These results indicate that the autocrine mechanism through EGFR may play an important role in the progression of infiltrating gross type of poorly differentiated adenocarcinoma of the stomach.

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